Medical Device Daily Senior Staff Writer

NEW ORLEANS  Frail, elderly patients with aortic stenosis who underwent a transcatheter aortic valve replacement (TAVR) procedure had about the same survival at one year as similar patients who had conventional open-heart surgery. But the TAVR patients were also more likely to have a stroke following the procedure, according to highly-anticipated preliminary data presented Sunday at American College of Cardiology's (ACC; Washington) 60th annual scientific session.

It's easy to understand the excitement about the PARTNER trial, sponsored by Edwards Lifesciences (Irvine, California), the company that makes the TAVR device. After all, given the choice between surgery or a non-surgical alternative most patients would prefer the latter.

"Large-scale, randomized comparisons of new interventional procedures to gold-standard surgical procedures have seldom been done," said Craig Smith, MD, chief of the Division of Cardiothoracic Surgery at New York-Presbyterian Hospital/Columbia University Medical Center, and the study's co-principal investigator. "This is the ideal opportunity, because surgical AVR is one of the most effective operations surgeons offer, and TAVR is the most exciting new treatment for aortic stenosis in the past two to three decades."

The TAVR device is a wire mesh stent encasing three sutured-on valve flaps called leaflets, made from cow tissue and treated to cut down on calcium deposits that cause stenosis. Cardiologists deliver the bioprosthetic valve to its target location with a catheter guided from a leg artery to the heart (transfemoral access; TF) or through the ribs (transapical access; TA) if peripheral arteries are not large enough. Like standard valve replacement, this procedure is performed under general anesthesia.

The researchers noted that TAVR significantly extended life expectancy and reduced hospital admissions in frail, elderly patients. Without valve replacement, prognosis is poor once symptoms appear. Cohort B of the PARTNER trial was designed to evaluate the effectiveness and cost-effectiveness of TAVR, also known as transcatheter aortic valve implantation (TAVI).

A total of 699 high-risk older patients with severe aortic stenosis were randomly assigned at 26 centers to TAVR or to conventional aortic valve replacement. The median age was 84.1 years. The TAVR group totaled 348 patients; 350 patients were in the surgical aortic valve replacement group. Patient characteristics were similar overall across cohorts, but the patients assigned to TA TAVR had a higher risk profile. Endpoints included death from any cause at one year (primary endpoint), stroke and major vascular and bleeding events.

When asked about superiority, Smith told reporters during an ACC press conference that the trial was not designed to show superiority and that it did not.

"This was an unusually old and sick patient population for a clinical trial," said Matthew Reynolds, MD, director of economics and quality of life research at Harvard Clinical Research Institute and a cardiologist for the VA Boston Healthcare System. "The mean age was 83, there was a very high prevalence of coronary artery disease and previous bypass surgery and about one-quarter had advanced lung disease. Despite this, the patients treated with TAVR did remarkably well."

When asked how many patients will be impacted by TAVR once it is FDA approved, Smith said "thousands" initially, and soon "tens of thousands" but that it would probably be several years before the impact reaches hundreds of thousands.

Cost-effectiveness results for the first year were based on detailed medical resource utilization data for all patients, and hospital billing data were collected for a subset of the patients. Long-term survival, quality-adjusted survival and costs were projected from the observed 12-month data to estimate the cost-effectiveness of TAVR over the full expected lifespan of the patients.

The initial cost for TAVR, along with care before and after the procedure (including both hospital and physician fees), was roughly $78,000, with the commercial cost for the new valve system estimated at about $30,000. The standard care group was three times more likely to be hospitalized for cardiovascular reasons than the TAVR group during the first year of follow-up. As a result, follow-up costs during the first year were roughly $23,000 higher for the standard care group.

The investigators projected a gain in life expectancy of about 1.9 years for the TAVR group over standard care (3.1 years vs. 1.2 years) at an incremental cost-effectiveness ratio of about $50,200 for each additional year of life gained, or about $62,000 per each quality-adjusted life year gained.

"For patients with severe aortic stenosis who are unsuitable for surgical valve replacement, TAVR significantly increases life expectancy at an incremental cost per life of year gained that is well within accepted values for commonly used cardiovascular technologies," Reynolds said. "Our perspective is that the costs of this intervention, even in this elderly and extremely high-risk population, are justified by the very significant benefits, and that the ratio of costs to benefits stacks up well compared with other therapies the U.S. healthcare system pays for today."

This is the first report from the randomized trial of aortic valve replacement vs. TAVR. In previously reported findings for patients in this trial who were not candidates for surgery, TAVR was linked to a 20% survival benefit at one year.

Although 30-day results favored TAVR for all-cause deaths (3.4% vs. 6.5%) and improvement in symptoms, both rates were similar at one year. Major strokes were higher for TAVR at both 30 days (3.8% vs. 2.1%) and one year (5.1% vs. 2.4%). At 30 days major vascular complications also were much more common after TAVR (11% vs. 3.2%), but the TAVR group's rates were much lower for major bleeding (9.3% vs. 19.5%) and new-onset irregular heart rhythms of atrial fibrillation (8.6% vs. 16%). Para-valvular regurgitation  leaks alongside or near the valve  occurred more often after TAVR as well.

"These results clearly show that TAVR is an excellent alternative to surgical AVR in high-risk patients," Smith said. "Recommendations to individual patients will need to weigh the appeal of avoiding open-heart surgery, with its known risks, against less invasive TAVR with different and less well understood risks, as well as the absence of long term follow-up. Future trials will help delineate the role of TAVR in intermediate risk patients."

A follow-up PARTNER II trial was approved in February to test the next generation of this new valve and a different catheter delivery system against the valve and delivery method used in the first PARTNER trial.

When asked about appropriate use and how he will talk to patients about this new option, Smith said "my story will not change" because already he is faced with explaining this procedure every day in the office. The important thing, he says, is to be honest with patients. "This doesn't have trivial risk . . . we have to be honest about what the risks are."

Once TAVR is approved, interventional cardiology specialist David Moliterno, MD, of the University of Kentucky (Lexington) agreed with Smith that it will be practice changing. "This is a historic event. It will change practice and it will lead to hundreds of thousands of patients [being impacted]," Moliterno said.

Ralph Brindis, president of ACC, agreed but also cautioned his colleagues in the field regarding dissemination of the new technology in order to ensure safety and efficacy for patients.

"This is a truly game-changing clinical trial. There are a huge amount of patients that are not getting therapy . . . it will take a while to ramp up experience in the centers, we as a profession have to be responsible," Brindis said. "This is a landmark technology; not everyone should be doing this . . . how can we as a society responsibly put together proper programs of diffusion of these new technologies?"

In fact, he suggested a mandated registry to make sure that new technology such as this, once it hits the market, reproduces the results expected based on the clinical trials.